Ignite Creation Date:
2024-06-16 @ 11:50 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06447987
Status:
RECRUITING
Last Update Posted:
2024-06-07
First Post:
2024-05-09
Brief Title:
Humanized CD19-Specific CAR T Cells for the Treatment of Patients With Positive Relapsed or Refractory CD19 Positive B-Cell Acute Lymphoblastic Leukemia
Sponsor:
City of Hope Medical Center
Organization:
City of Hope Medical Center
Study Overview
Official Title:
Phase Ib Study to Evaluate Humanized CD19-Specific CAR T Cells Following Lymphodepleting Chemotherapy in Adult Patients With RelapsedRefractory CD19 B-Cell Acute Lymphoblastic Leukemia
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase Ib trial tests the safety side effects and effectiveness of humanized huCD19-chimeric antigen receptor CAR T cell therapy in treating patients with CD19 positive B-cell acute lymphoblastic leukemia ALL that has come back after a period of improvement relapsed or that has not responded to previous treatment refractory CAR T-cell therapy is a treatment in which a patients T cells a type of immune system cell are changed in the laboratory so they will attack cancer cells T cells are taken from a patients blood Then the gene for a special receptor that binds to a certain protein such as CD19 on the patients cancer cells is added to the T cells in the laboratory The special receptor is called a chimeric antigen receptor CAR Large numbers of the huCD19 positive CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers Chemotherapy drugs such as fludarabine and cyclophosphamide work in different ways to stop the growth of cancer cells either by killing the cells by stopping them from dividing or by stopping them from spreading huCD19-CAR T cell therapy may be safe tolerable and effective in treating patients with relapsed or refractory CD19 positive ALL
Detailed Description:
PRIMARY OBJECTIVES
I Assess the safety and tolerability of Tnmem-enriched huCD19VH4VK1dCH2BBzetaEGFRt T cells huCD19 CAR T as single-dose monotherapy by evaluation of toxicities including type frequency severity attribution time course and duration
II Determine the maximum feasible dose MFDrecommended phase 2 doses schedule RP2D of huCD19 CAR T as single-dose monotherapy on relapsedrefractory rr ALL patients
SECONDARY OBJECTIVES
I Obtain preliminary estimates of complete remission complete remission CR complete response with incomplete bone marrow recovery CRi rates
II Overall response rate CR CRi best response III Duration of response CR CRi IV Minimal residual disease MRD- negative CRCRi V The number and rate of bridging to transplant VI Estimate the progression free survival PFS and overall survival OS rate at 6-months and 1-year post first huCD19 CAR T cell infusion
EXPLORATORY OBJECTIVES
I Access the expansion and persistence of T cell via flow cytometry in blood bone marrow BM and cerebrospinal fluid CSF
II Assess the phenotype and activation status of CAR T via flow cytometry polymerase chain reaction PCR and cytokine analysis
III Assess CAR T cell clonal expansion and repertoires of endogenous T cells IV Assess immunophenotyping and functional analyses of CAR T cell products V Determine the role of the immunologic milieu VI Evaluation of B cell aplasia VII Serum cytokine measurement VIII Tumor antigen analysis XIV Evaluation of Immunogenicity by enzyme-linked immunosorbent assay ELISA X For subjects who receive cetuximab for CAR T cell ablation assess the activity of infusional cetuximab to eliminate transferred huCD19-CAR T cells
OUTLINE This is a dose-escalation study of huCD19-CAR T followed by a dose-expansion study
Patients undergo leukapheresis then receive lymphodepletion chemotherapy with fludarabine ntravenously IV and cyclophosphamide IV on days -5 -4 and -3 and huCD19-CAR T IV cells over 10-15 minutes on day 0 Patients may optionally receive cetuximab IV over 60-120 minutes at least 28 days post T cell infusion and undergo allogeneic hematopoietic cell transplantation alloHCT Additionally patients undergo echocardiography ECHO or multigated acquisition scan MUGA computed tomography CT or positron emission tomography PETCT and optional magnetic resonance imaging MRI on study and bone marrow biopsy and aspiration and blood sample collection throughout the study
After completion of study treatment patients are followed up monthly for 1 year then yearly for up to 15 years
I Assess the safety and tolerability of Tnmem-enriched huCD19VH4VK1dCH2BBzetaEGFRt T cells huCD19 CAR T as single-dose monotherapy by evaluation of toxicities including type frequency severity attribution time course and duration
II Determine the maximum feasible dose MFDrecommended phase 2 doses schedule RP2D of huCD19 CAR T as single-dose monotherapy on relapsedrefractory rr ALL patients
SECONDARY OBJECTIVES
I Obtain preliminary estimates of complete remission complete remission CR complete response with incomplete bone marrow recovery CRi rates
II Overall response rate CR CRi best response III Duration of response CR CRi IV Minimal residual disease MRD- negative CRCRi V The number and rate of bridging to transplant VI Estimate the progression free survival PFS and overall survival OS rate at 6-months and 1-year post first huCD19 CAR T cell infusion
EXPLORATORY OBJECTIVES
I Access the expansion and persistence of T cell via flow cytometry in blood bone marrow BM and cerebrospinal fluid CSF
II Assess the phenotype and activation status of CAR T via flow cytometry polymerase chain reaction PCR and cytokine analysis
III Assess CAR T cell clonal expansion and repertoires of endogenous T cells IV Assess immunophenotyping and functional analyses of CAR T cell products V Determine the role of the immunologic milieu VI Evaluation of B cell aplasia VII Serum cytokine measurement VIII Tumor antigen analysis XIV Evaluation of Immunogenicity by enzyme-linked immunosorbent assay ELISA X For subjects who receive cetuximab for CAR T cell ablation assess the activity of infusional cetuximab to eliminate transferred huCD19-CAR T cells
OUTLINE This is a dose-escalation study of huCD19-CAR T followed by a dose-expansion study
Patients undergo leukapheresis then receive lymphodepletion chemotherapy with fludarabine ntravenously IV and cyclophosphamide IV on days -5 -4 and -3 and huCD19-CAR T IV cells over 10-15 minutes on day 0 Patients may optionally receive cetuximab IV over 60-120 minutes at least 28 days post T cell infusion and undergo allogeneic hematopoietic cell transplantation alloHCT Additionally patients undergo echocardiography ECHO or multigated acquisition scan MUGA computed tomography CT or positron emission tomography PETCT and optional magnetic resonance imaging MRI on study and bone marrow biopsy and aspiration and blood sample collection throughout the study
After completion of study treatment patients are followed up monthly for 1 year then yearly for up to 15 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2024-03338 | REGISTRY | None | None |
| 23328 | OTHER | None | None |
| P30CA033572 | NIH | City of Hope Medical Center | httpsreporternihgovquickSearchP30CA033572 |